The present invention relates to a microbiological method for the stereoselective reduction of the 15-keto function in bicyclic prostaglandin intermediates to the corresponding 15-hydroxy compounds, viz., in such a manner that the resultant 15-hydroxy group, as well as an original 11-hydroxy group, are in the 60-position.
Although the chemical reduction of 15-keto groups in prostaglandins and progstaglandin intermediates, for example with sodium borohydride, produces the desired 15.alpha.-hydroxyprostaglandins, it does so only by way of mixtures of the corresponding 15.alpha.- and 15.beta.-hydroxy compounds and only with the concomitant losses in yield which accompany the subsequent separating procedure thereby required. This problem has been somewhat alleviated by disclosure of a series of microorganisms (U.S. Pat. No. 3,687,811) which permit conversion of the 15-keto group in 11-hydroxy-15-oxoprostaglandins to the corresponding trans-15-hydroxy group, its exact conformation depending on the original conformation of the 11-hydroxy group. Also, from DOS (German Unexamined Laid-Open Application) No. 2,357,815 or from the corresponding U.S. Pat. No. 3,799,841, there is known a microbiological method for converting, for example, an 11-hydroxy-15-oxoprostaglandin into a mixture of 11.alpha., 15.alpha.- and 11.beta.-, 15.beta.-dihydroxyprostaglandins. This cis arrangement of the 11.alpha., 15.alpha.-hydroxy groups is especially advantageous in that it corresponds to that of biologically active prostaglandins.
All these aforementioned processes, however, fail when applied to the microbiological reduction of (1S,5R,6R,7R)-6-[(E)-3-oxophenoxy-1-alkenyl]-7-hydroxy-2-oxabicyclo[3,3,0] octan-3-ones. Furthermore, the microbiological process described in DOS 2,401,761 or in the corresponding British Pat. No. 1 430 191 achieves only very low yields. In addition, this process has the disadvantage that the basidiomycetes employed for the reduction exhibit only a slow growth and cannot be handled readily since they are higher fungi.